The Pilot Studies Program continues to play a crucial role in promoting the UCONN ARC'S vitality and growth. During the past 5 years, several innovative studies including: (1) microRNA regulation of HTR1B gene expression; (2) exercise as a behavioral intervention for hazardous drinking in college students; (3) examining genes that may affect problem drinking and obesity risk; and (4) examining the safety and efficacy of dutasteride as a treatment for heavy drinking were supported. One of these projects inspired a major component of this Center renewal application. Others have led, or are likely to lead, to applications for other types of extramural support. The Pilot Studies Program will continue to be managed by the PI and Executive Committee in consultation with internal and external advisors. Following an open call for proposals, applications will be reviewed to: (1) judge scientific merit; (2) improve the quality of the research through feedback, revision, and mentorship (if needed); (3) create a system whereby resources are allocated fairiy and equitably; and (4) ensure that the research meets ethical standards. Several projects are proposed. The first project will examine dermal fibroblasts, sampled from alcoholdependent and non-dependent subjects that are reprogrammed into induced pluripotent stem (iPS) cells and differentiated into neurons. The goal is to detect changes in NMDA receptor and GABAergic signaling in response to acute and chronic alcohol exposure. A second project will survey the fidelity and acceptance of Contingency Management for alcohol dependence as it is disseminated in clinical settings throughout the VA health care system. The third project will take advantage of the screening, brief intervention and referral to treatment (SBIRT) initiative mandated by JCAHO and CMS for hospitals in New England, including UCHC. This study will develop process measures needed to evaluate the mechanisms of change attributable to factors other than the intervention. Projects proposed for the out years will be designed around new alcohol research collaborations being developed with the Connecticut Department of Corrections, the Jackson Laboratories' personalized medicine research facility now under construction on our campus.